Document Detail

Effects of endothelin-1 on vascular permeability in the conscious rat: interactions with platelet-activating factor.
MedLine Citation:
PMID:  1667286     Owner:  NLM     Status:  MEDLINE    
1. The objectives of the present experiments were to assess the effects of endothelin-1 on the macrovascular permeability in selected vascular beds, to study the involvement of platelet-activating factor (PAF) in vascular responses to endothelin-1 and to examine the vascular effects of combined administration of endothelin-1 and PAF in conscious rats. 2. Intravenous bolus injection of endothelin-1 (0.1-2 nmol kg-1) resulted in a dose-dependent biphasic change in mean arterial blood pressure (MABP) with initial transient hypotension followed by a prolonged pressor action. These changes were accompanied by a dose-dependent increase in haematocrit values. 3. Endothelin-1 (0.1 and 1 nmol kg-1) increased dose-dependently the vascular permeability of the trachea, upper and lower bronchi, stomach, duodenum, spleen and kidney (up to 240%) as measured by the extravasation of Evans blue dye. The permeability of pulmonary parenchyma, liver and pancreas was not affected significantly by endothelin-1 treatment. 4. Pretreatment of animals with the specific PAF receptor antagonist, WEB 2086 (1 mg kg-1, i.v.) or BN 52021 (10 mg kg-1, i.v.) reduced the endothelin-1 (1 nmol kg-1)-induced rise in haematocrit by about 50 and 30%, respectively. Both antagonists were highly effective at inhibiting protein extravasation in the stomach, duodenum and kidney. On the other hand, BN 52021, but not WEB 2086, significantly attenuated the effect of endothelin-1 on permeability in the lower bronchi and spleen. Neither WEB 2086 nor BN 52021 modified the changes in MABP evoked by endothelin-1.5. When low doses of endothelin-1 (0.1 nmolkg-')and PAF (0.19nmolkg-')were administered simultaneously, enhanced protein extravasation was detected in the upper and lower bronchi, whereas neither endothelin-1 nor PAF by themselves affected vascular permeability in these tissues. These changes occurred in the absence of significant changes in MABP.6. Combined administration of higher doses of endothelin-1 (1nmolkg-') and PAF (1.9nmolkg-') resulted in marked increases (up to 530%) in protein extravasation in the airways, pancreas, stomach and duodenum. The effect of endothelin-1 on permeability was not affected by PAF in the spleen, whereas it was completely inhibited by PAF in the kidney. Combined injection of endothelin-1 and PAF resulted in a slight, but significant increase in MABP.7. The present findings show that endothelin-1 is capable of increasing vascular permeability in selected vascular beds including the airways, gastrointestinal tract and kidney, and suggest that PAF may mediate, in part, its action on permeability, but not its hypotensive action. The present data also suggest that endothelin-1 and PAF can act in concert to increase vascular permeability in rat airways and gastrointestinal tract.
J G Filep; M G Sirois; A Rousseau; A Fournier; P Sirois
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  British journal of pharmacology     Volume:  104     ISSN:  0007-1188     ISO Abbreviation:  Br. J. Pharmacol.     Publication Date:  1991 Dec 
Date Detail:
Created Date:  1992-06-03     Completed Date:  1992-06-03     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  7502536     Medline TA:  Br J Pharmacol     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  797-804     Citation Subset:  IM    
Department of Pharmacology, Faculty of Medicine, University of Sherbrooke, Canada.
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MeSH Terms
Azepines / pharmacology
Blood Pressure / drug effects
Capillary Permeability / drug effects*
Endothelins / pharmacology*
Lactones / pharmacology
Platelet Activating Factor / antagonists & inhibitors,  pharmacology*
Platelet Membrane Glycoproteins*
Rats, Inbred Strains
Receptors, Cell Surface / antagonists & inhibitors
Receptors, G-Protein-Coupled*
Triazoles / pharmacology
Reg. No./Substance:
0/Azepines; 0/Diterpenes; 0/Endothelins; 0/Ginkgolides; 0/Lactones; 0/Platelet Activating Factor; 0/Platelet Membrane Glycoproteins; 0/Receptors, Cell Surface; 0/Receptors, G-Protein-Coupled; 0/Triazoles; 0/platelet activating factor receptor; 105219-56-5/WEB 2086; 99796-69-7/ginkgolide B

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